Lesions are normally defined as an abnormal tissue structure located in an organ or other body part, and are often a manifestation of a harmful condition, disease or illness. Lesions may take many specific forms, such as choroidal neovascularizations (“CNVs”) which are found in the eye. In general, any abnormal vasculature in a body is a type of lesion.
Lesions must often be identified and visualized prior to treatment and such methods are known in the art. For example, CNVs are routinely visualized using indocyanine green (“ICG”) dye angiography (“ICGA”). It is based on use of the near-infrared fluorescent light wavelengths emitted by ICG, which readily penetrate the pigmented ocular tissues. Methods for enhancing visualization of CNVs (i.e. as taught in U.S. Pat. No. 5,394,199) are also known in the art.
Traditionally, CNVs were treated by destruction of the entire CNV membrane using photocoagulation. Photocoagulation involves the application of energy, such as through a laser, sufficient to reduce the flow of blood through a target vessel or tissue. Photocoagulation of an entire CNV, however, involved the destruction of a significant portion of the retina. Advances in the visualization of CNVs allowed for the ability to perform high-speed imaging. This led to the development of a current AMD treatment modality, namely CNV feeder vessel photocoagulation treatment.
Following visualization of a CNV feeder vessel (e.g. by ICGA), feeder vessel photocoagulation is performed by photocoagulating an afferent vessel supplying blood to a CNV. This reduces or stops the flow of blood to the CNV. With feeder vessel photocoagulation, an often smaller fundus area is photocoagulated since only the feeder vessel is targeted even when the CNV itself may be relatively large in area. Also, the photocoagulation is often removed from the CNV, which may be juxta- or sub-foveal, thereby avoiding photocoagulation related damage to the fovea.
One feeder vessel photocoagulation methodology also involves the use of a radiation absorbing dye, such as ICG. The presence of the radiation absorbing dye in a target blood vessel enhances the uptake of near-infrared laser energy and decreases the amount of laser energy required to photocoagulate the targeted vessel and is referred to as Dye-Enhanced Photocoagulation (“DEP”). Thus, DEP reduces the amount of concomitant damage to the overlying sensory retina.
Another example of a current method for treating abnormal vasculature is photodynamic therapy (“PDT”). Generally, application of PDT requires administration of a photodynamic agent into a subject, typically by intra-venous injection. Once the agent arrives in a target site containing a tissue to be treated, the site is subjected to energy, e.g. light of a certain wavelength generated by a laser causing excitation of the agent. When the agent is excited, it produces oxygen radicals which then attack the cells of the surrounding tissue, resulting in degradation of those cells. By way of example, and in the case of CNV, PDT destroys vascular endothelial cells of the CNV. This reduces, and preferably halts, the flow of blood within the CNV.
It is possible that in some cases, reperfusion occurs following initially successful PDT of a CNV. PDT treatment may thus require multiple applications. Moreover, it now appears that the extent to which many PDT agents are selective for abnormal vasculature may not be as high as originally expected. In other words, concentration of PDT agent in the blood, rather than binding of PDT agent to the endothelium, is more determinative of efficacy of PDT treatment. As a result, the non-target areas of the fundus may be subjected to more PDT-mediated damage than originally anticipated. Also, PDT therapy traditionally involves infusing the PDT agent into a subject's vasculature, typically over about a ten (10) minute period. Infusion requires large quantities of PDT agent. Large quantities of PDT agent also translate into an increase in the likelihood of side effects, higher total cost and more light sensitivity post-treatment.
A need exists for improved methods of treatment of age-related macular degeneration associated choroidal neovascularizations and lesions generally.